Sodium Carbonate → 5-chloro-1-methyl-1H-imidazole-4-carbaldehyde

Phosphoryl trichloride (1 mL, 11 mmol) was added slowly to a 0° C. solution of DMF (22 mL), followed by 2-amino-N-methylacetamide hydrochloride (2.5 g, 20 mmol). The mixture was warmed at room temperature and stirred at 60° C. before phosphoryl trichloride (35 mL, 390 mmol) was added slowly. The solution was stirred at 90° C. overnight. After cooling to room temperature, the mixture was poured into ice/water (500 mL). Solid sodium carbonate was added until pH 6-7 was reached. The mixture was extracted with DCM (4×150 mL). The organic extracts were combined, dried over MgSO4, filtered, evaporated, and dried in vacuo. The residue was dissolved in water (10 mL) and 1,4-dioxane (20 mL) before potassium carbonate (10 g, 72.3 mmol) was added. The mixture was stirred at 60° C. for 4 hours. The mixture was evaporated to dryness. The residue was treated with 50% EtOAc/Et2O (250 mL). The solid was removed by filtration. The filtrate was recovered, evaporated, and dried in vacuo, affording 5-chloro-1-methyl-1H-imidazole-4-carbaldehyde (476 mg, 23% yield). The product was used without further purification.

1. additionwas added slowly
2. temperatureAfter cooling to room temperature
3. extractionThe mixture was extracted with DCM (4×150 mL)
4. dry with materialdried over MgSO4
5. filtrationfiltered
6. customevaporated
7. customdried in vacuo
8. dissolutionThe residue was dissolved in water (10 mL)
9. stirringThe mixture was stirred at 60° C. for 4 hours
10. customThe mixture was evaporated to dryness
11. additionThe residue was treated with 50% EtOAc/Et2O (250 mL)
12. customThe solid was removed by filtration
13. customThe filtrate was recovered
14. customevaporated
15. customdried in vacuo

ORD record

ord-de53dc0e1fb949faad2db6a08c08fd1b

Source dataset

uspto-grants-2016_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09315521B2